NCT02242266

Completed

Phase 2

A Single Dose, Placebo-controlled, Randomized, Double-blind, Double-dummy, Crossover Efficacy, Pharmacokinetics and Safety Comparison of Tiotropium Inhalation Powder (5 μg and 10 μg), Administered as the Bromide Salt From Hard Polyethylene Capsule Via the HandiHaler® 2 and Spiriva® HandiHaler® (18 μg Tiotropium) in Patients With Chronic Obstructive Pulmonary Disease (COPD)

Boehringer Ingelheim0 sites121 target enrollmentJuly 28, 2005

ConditionsPulmonary Disease, Chronic Obstructive

InterventionsTiotropium low dose Placebo via the grey HandiHaler®Tiotropium medium dose Spiriva® HandiHaler® high dose Placebo via the blue HandiHaler®

DrugsPlacebo via the grey HandiHaler®Tiotropium low dose Tiotropium medium dose Spiriva® HandiHaler® high dose Placebo via the blue HandiHaler®

Overview

Phase: Phase 2
Intervention: Tiotropium low dose
Conditions: Pulmonary Disease, Chronic Obstructive
Sponsor: Boehringer Ingelheim
Enrollment: 121
Primary Endpoint: Area under the curve for the time period 0 to 12 hours of forced expiratory volume in one second (FEV1 AUC0-12)
Status: Completed
Last Updated: 2 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Similar Trials

Overview

Brief Summary

The primary objective of this trial was to establish non-inferiority of lung function response to tiotropium 10 μg, formulated as inhalation powder in the polyethylene hard capsule and delivered via the HandiHaler® 2, compared to tiotropium 18 μg, formulated as inhalation powder in the hard gelatine capsule and delivered via the HandiHaler® (Spiriva®) following single dose inhalation in patients with COPD. A hard polyethylene (PE) capsule with half the strength (tiotropium 5 μg) was included to investigate a dose ordering effect.

The secondary objectives were to characterize the pharmacokinetics of tiotropium inhalation powder hard PE capsule (delivered via HandiHaler® 2) and tiotropium inhalation powder hard gelatine capsule (delivered via HandiHaler®) and to compare the safety of the two pharmaceutical formulations.

Registry

clinicaltrials.gov

Start Date

July 28, 2005

End Date

June 4, 2006

Last Updated

2 years ago

Study Type

Interventional

Study Design

Crossover

Sex

All

Investigators

Sponsor

Boehringer Ingelheim

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•All patients must sign an informed consent consistent with International Conference on Harmonization Good Clinical Practice (ICH-GCP) guidelines and local legislations prior to any study-related procedures, which includes medication washout and restrictions
•All patients must have a diagnosis of chronic obstructive pulmonary disease and must meet the following spirometric criteria:
•Patients must have relatively stable\* airway obstruction with a pre-dose FEV1 \<= 60% of predicted normal and FEV1 \<= 70% of FVC at Visits 1 and
•\* The randomization of patients with any respiratory infection or COPD exacerbation in the 6 weeks prior to the Screening Visit (Visit 1) or during the baseline period should be postponed. Patients may be randomized 6 weeks following recovery from the infection or exacerbation
•At Visit 1, patients must demonstrate an improvement in FEV1 of \>= 12% over the baseline FEV1 value 45 minutes after inhalation of 4 puffs of 20 µg ipratropium bromide (Atrovent® MDI)
•Male or female patients 40 years of age or older
•Patients must be current or ex-smokers with a smoking history of more than 10 pack-years (Patients who had never smoked cigarettes had to be excluded)
•Patients must be able to perform technically acceptable pulmonary function tests during the study period as required in the protocol
•Patients must be able to inhale medication in a competent manner from the HandiHaler® 2 and the HandiHaler® devices

Exclusion Criteria

•Patients with significant diseases other than COPD will be excluded. A significant disease is defined as a disease which in the opinion of the investigator may either put the patient at risk because of participation in the study or a disease which may influence the results of the study or the patient's ability to participate in the study
•Patients with a recent history (i.e., six months or less) of myocardial infarction
•Patients who have been hospitalized for heart failure (NYHA class III or IV) within the past year
•Patients with any unstable or life threatening cardiac arrhythmia or cardiac arrhythmia requiring intervention or a change in drug therapy within the past year
•Patients with malignancy for which the patient has undergone resection, radiation therapy or chemotherapy within the last five years. Patients with treated basal cell carcinoma are allowed
•Patients with a history of asthma, allergic rhinitis or atopy or who have a total blood eosinophil count ≥600/mm
•A repeat eosinophil count will not be conducted in these patients
•Patients with a history of life threatening pulmonary obstruction, or a history of cystic fibrosis or clinically evident bronchiectasis
•Patients with known active tuberculosis
•Patients with significant alcohol or drug abuse within the past two years

Arms & Interventions

Tiotropium low dose

oral inhalation via the blue HandiHaler®

Intervention: Tiotropium low dose

Tiotropium low dose

oral inhalation via the blue HandiHaler®

Intervention: Placebo via the grey HandiHaler®

Tiotropium medium dose

oral inhalation via the blue HandiHaler®

Intervention: Tiotropium medium dose

Tiotropium medium dose

oral inhalation via the blue HandiHaler®

Intervention: Placebo via the grey HandiHaler®

Spiriva® HandiHaler® high dose

oral inhalation via the grey HandiHaler®

Intervention: Spiriva® HandiHaler® high dose

Spiriva® HandiHaler® high dose

oral inhalation via the grey HandiHaler®

Intervention: Placebo via the blue HandiHaler®

Placebo

Intervention: Placebo via the blue HandiHaler®

Placebo

Intervention: Placebo via the grey HandiHaler®

Outcomes

Primary Outcomes

Area under the curve for the time period 0 to 12 hours of forced expiratory volume in one second (FEV1 AUC0-12)

Time Frame: pre-dose and 30, 60 minutes, 2, 3, 4, 6, 8, 10 and 12 hours post-dosing

Secondary Outcomes

Peak FEV1 on each test-day(pre-dose and 30, 60 minutes, 2 and 3 hours post-dosing)
Peak forced vital capacity (FVC)(pre-dose and 30, 60 minutes, 2, 3, 4, 6, 8, 10, 12, 14, 22, 23 and 24 hours post-dosing)
FVC AUC0-12(pre-dose and 30, 60 minutes, 2, 3, 4, 6, 8, 10 and 12 hours post-dosing)
FEV1 AUC12-24(12, 14, 22, 23 and 24 hours post-dosing)
FVC AUC0-24(pre-dose and 30, 60 minutes, 2, 3, 4, 6, 8, 10, 12, 14, 22, 23 and 24 hours post-dosing)
FEV1 AUC0-24(pre-dose and 30, 60 minutes, 2, 3, 4, 6, 8, 10, 12, 14, 22, 23 and 24 hours post-dosing)
Individual FEV1 measurements at each time point(pre-dose and 30, 60 minutes, 2, 3, 4, 6, 8, 10, 12, 14, 22, 23 and 24 hours post-dosing)
FVC AUC12-24(12, 14, 22, 23 and 24 hours post-dosing)
Individual FVC measurements at each time point(pre-dose and 30, 60 minutes, 2, 3, 4, 6, 8, 10, 12, 14, 22, 23 and 24 hours post-dosing)
AUCt1-t2 (area under the concentration-time curve of the analyte in plasma over the time interval t1 to t2)(5, 15, 30 minutes, 1 and 2 hours following drug administration)
Cmax (maximum measured concentration of the analyte in plasma)(5, 15, 30 minutes, 1 and 2 hours following drug administration)
tmax (time from dosing to the maximum concentration of the analyte in plasma)(5, 15, 30 minutes, 1 and 2 hours following drug administration)
Aet1-t2 (amount of analyte that is eliminated in urine from the time point t1 to time point t2)(0 to 2, 2 to 12 hours after administration)
fet1-t2 (fraction of analyte eliminated in urine from time point t1 to time point t2)(0 to 2, 2 to 12 hours after administration)
%AUCtz-∞ (percentage of the extrapolated part of the total AUC0-∞)(5, 15, 30 minutes, 1 and 2 hours following drug administration)
CLR,t1-t2 (renal clearance of the analyte from the time point t1 until the time point t2)(0 to 2, 2 to 12 hours after administration)
Number of patients with adverse events(up to 13 weeks)